This is a multifaceted program concerning the measurement of regional myocardial blood flow per gram of tissue, determination of the relationship between local blood flow and certain local metabolism functions, and implications of this heterogeneity with respect to the transport of material through the vascular system. This program is designed to develop a comprehensive data base and conceptual approach to intravascular transport which will serve as a framework upon which the kinetics of blood-tissue exchange of various solutes (hydrophilic, lipophilic and gaseous) can be based. There are five main aims. The first is to develop and document the utility of a plasma-soluble marker for the measurement of regional blood flow within the heart. In the initial trials we use desmethylimipramine whose deposition is as good as microspheres, 98% or more retention in the first minute at normal flows. The second aim is to use the best available plasma-soluble marker as a "gold standard" against which to test the adequacy of microsphere deposition densities for the estimation of flows in small regions and for ventricular transmural distributions. The third aim is to compare regional substrate uptake (fatty acids, glucose) with regional flows, in order to gain insight into the basis for the broad heterogeneity of myocardial flows. The fourth aim is to obtain a comprehensive set of data on the transport delay and dispersion of an intravascular indicator using both outflow detection following bolus injection and detection of the heart's residual content of gamma-emitting tracers, using deposition of microspheres or of the plasma-soluble flow marker to define the heterogeneity; in order to separate large vessel and capillary transport, the transport of a highly diffusible tracer, iodoantipyrine, which is flow-limited in its blood-tissue exchange, is obtained simultaneously. The fifth aim is to develop a new technique to estimate the degree of heterogeneity from outflow dilution curves for continuously detectable non-isotopic markers, ascorbate and indocyanine green, to characterize the heterogeneity and to develop microvascular network models that might describe and explain it, in varied physiological states. The five groups of projects provide a broad set of physiological and anatomic data on coronary blood flow and the basis of its heterogeneity; the data and concepts are important to understanding blood-tissue exchange kinetics in the heart and other organs.